کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2189689 | 1096219 | 2006 | 20 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Structural Basis of Carbohydrate Transfer Activity by Human UDP-GalNAc: Polypeptide α-N-Acetylgalactosaminyltransferase (pp-GalNAc-T10) Structural Basis of Carbohydrate Transfer Activity by Human UDP-GalNAc: Polypeptide α-N-Acetylgalactosaminyltransferase (pp-GalNAc-T10)](/preview/png/2189689.png)
Mucin-type O-glycans are important carbohydrate chains involved in differentiation and malignant transformation. Biosynthesis of the O-glycan is initiated by the transfer of N-acetylgalactosamine (GalNAc) which is catalyzed by UDP-GalNAc:polypeptide α-N-acetylgalactosaminyltransferases (pp-GalNAc-Ts). Here we present crystal structures of the pp-GalNAc-T10 isozyme, which has specificity for glycosylated peptides, in complex with the hydrolyzed donor substrate UDP-GalNAc and in complex with GalNAc–serine. A structural comparison with uncomplexed pp-GalNAc-T1 suggests that substantial conformational changes occur in two loops near the catalytic center upon donor substrate binding, and that a distinct interdomain arrangement between the catalytic and lectin domains forms a narrow cleft for acceptor substrates. The distance between the catalytic center and the carbohydrate-binding site on the lectin β sub-domain influences the position of GalNAc glycosylation on GalNAc-glycosylated peptide substrates. A chimeric enzyme in which the two domains of pp-GalNAc-T10 are connected by a linker from pp-GalNAc-T1 acquires activity toward non-glycosylated acceptors, identifying a potential mechanism for generating the various acceptor specificities in different isozymes to produce a wide range of O-glycans.
Journal: Journal of Molecular Biology - Volume 359, Issue 3, 9 June 2006, Pages 708–727